A functional Calcitonin Gene Related Peptide (CGRP) receptor requires dimerization of Calcitonin Receptor-Like Receptor (CRLR) with Receptor Activity Modifying Protein 1 (RAMP 1). To determine the function of the three domains (extracellular ECD, transmembrane TM, and tail domains) of human RAMP 1, three mutants were constructed: RAMP 1 without the cytoplasmic tail, a chimera consisting of the ECD of RAMP 1 and the TM and tail of the Platelet Derived Growth Factor receptor and the ECD of RAMP 1 alone. These RAMP1 mutants were examined for their ability to associate with CRLR to effect CGRP stimulated cAMP accumulation, CGRP binding, CRLR trafficking and cell surface expression. All RAMP 1 mutants were able to associate with CRLR with full efficacy for CGRP stimulated cAMP accumulation. However, the RAMP1/PDGFR chimera demonstrated a 10-fold decrease in potency for CGRP signaling and binding, and the RAMP 1 ECD mutant had a 4000-fold decrease in potency. In conclusion, the ECD of RAMP 1 is sufficient for normal CRLR association and efficacy. The presence of a TM domain and the specific sequence of the RAMP1 TM domain contribute to CGRP affinity and potency. The C-terminal tail of RAMP 1 is unnecessary for CRLR function.